Livsey Jacqueline E, Cowan Richard A, Wylie James P, Swindell Ric, Read Graham, Khoo Vincent S, Logue John P
Department of Clinical Oncology, Christie Hospital NHS Trust, Manchester, England, United Kingdom.
Int J Radiat Oncol Biol Phys. 2003 Dec 1;57(5):1254-9. doi: 10.1016/s0360-3016(03)00752-1.
Recent publications have indicated that the alpha/beta ratios for carcinoma of the prostate are much lower than had originally been thought, suggesting that prostate cancer may be highly sensitive to fraction size. We have reviewed our unique experience of the use of 3.13 Gy fractions in a large cohort of men treated homogeneously in a single institute.
The outcome for 705 men with T1-T4, N0, M0 prostate cancer who received conformal radiotherapy between 1995 and 1998 at this center was analyzed. No patient received hormonal manipulation. Mean age was 68 years (range: 49-84 years). Median pretreatment PSA was 13 ng/mL (range: 0.6-270 ng/mL). Disease characteristics were as follows: Stage T1, 125 (18%); T2, 365 (52%); T3/4, 215 (30%); Gleason 2-6, 463 (66%); Gleason 7-10, 242 (34%); pretreatment PSA < or =10 ng/mL, 291 (41%); 10 to < or =20, 228 (32%); >20, 186 (27%). Median follow-up was 48 months (range: 1-82 months). Biochemical-free survival (bNED) was defined by the American Society for Therapeutic Radiology and Oncology consensus definition. Radiotherapy was delivered to a planning target volume (prostate plus all/base of the seminal vesicles dependent on risk criteria with a 1-cm margin) with a 4-field conformal technique to a dose of 50 Gy in 16 daily fractions over 22 days.
The 5-year bNED survival was significantly associated (p < 0.001) with pretreatment PSA, stage, and Gleason score. Five-year bNED rates with respect to pretreatment characteristics were as follows: 73% (PSA < or =10), 52% (>10-20), 35% (>20), 64% (Stage T1/2), 38% (T3/4), 61% (Gleason score 2-6), and 46% (Gleason > or =7). When patients were grouped into good (Stage T1/2, PSA < or =10 ng/mL, and Gleason score <7) (n = 181), intermediate (1 raised value) (n = 247), or poor (2 or more raised values) (n = 277) prognostic groups, the bNED was, respectively, 82%, 56%, and 39%. Radiation Therapy Oncology Group Grade > or =2 bowel toxicity was 5% and bladder 9%.
These data indicate that the delivery of a relatively low total dose using a hypofractionated regime results in similar tumor control and normal-tissue toxicity to 65-70 Gy delivered in 1.8-2 Gy fractions. These data suggest that this is an acceptable regime for good-prognosis patients. However, because of the evidence for a dose effect at doses above 70 Gy with "conventional fractionation," we are now treating intermediate- and poor-risk patients within a hypofractionated dose escalation trial to 60 Gy in 20 fractions using intensity- modulated radiotherapy.
近期发表的文献表明，前列腺癌的α/β比值远低于最初的设想，这提示前列腺癌可能对分次剂量高度敏感。我们回顾了在单一机构对一大群男性患者均匀使用3.13 Gy分次剂量的独特经验。
分析了1995年至1998年期间在本中心接受适形放疗的705例T1 - T4、N0、M0期前列腺癌男性患者的治疗结果。所有患者均未接受激素治疗。平均年龄为68岁（范围：49 - 84岁）。治疗前前列腺特异性抗原（PSA）中位数为13 ng/mL（范围：0.6 - 270 ng/mL）。疾病特征如下：T1期，125例（18%）；T2期，365例（52%）；T3/4期，215例（30%）；Gleason评分2 - 6分，463例（66%）；Gleason评分7 - 10分，242例（34%）；治疗前PSA≤10 ng/mL，291例（41%）；10至≤20 ng/mL，228例（32%）；＞20 ng/mL，186例（27%）。中位随访时间为48个月（范围：1 - 82个月）。无生化复发生存（bNED）根据美国放射肿瘤学会的共识定义确定。采用4野适形技术将放疗剂量给予计划靶体积（前列腺加根据风险标准确定的所有/精囊底部，并外放1 cm边界），剂量为50 Gy，分16次每日照射，共22天。
5年bNED生存率与治疗前PSA、分期和Gleason评分显著相关（p＜0.001）。根据治疗前特征的5年bNED率如下：PSA≤10时为73%，＞10至≤20时为52%，＞20时为35%；T1/2期为64%，T3/4期为38%；Gleason评分2 - 6分时为61%，Gleason≥7分时为46%。放射肿瘤学组≥2级肠道毒性发生率为5%，膀胱毒性发生率为9%。
这些数据表明，采用大分割方案给予相对较低的总剂量，与以1.8 - 2 Gy分次给予至65 - 70 Gy相比，在肿瘤控制和正常组织毒性方面相似。这些数据表明，对于预后良好患者，这是一种可接受的方案。然而，鉴于有证据表明在“常规分割”情况下，剂量超过70 Gy存在剂量效应，我们目前正在通过调强放疗在大分割剂量递增试验中对中危和高危患者进行治疗，剂量递增至60 Gy，分20次照射。
